The past decade has experience a flurry of excitement related to the prospect of preventing HIV infection, and reaching an AIDS free generation, using a spectrum of different interventions including microbicides, PREP, voluntary circumcision, and prevention of mother to child transmission. However, vaccines are the most cost-effective mode of prevention of infections to date. Thus on the prevention landscape, vaccines can make an incredible additional mechanism by which to end this epidemic. Dr. Bart Haynes, Director of the Center for HIV/AIDS Vaccine Immunology- Immunogen Design (CHAVI-ID) from Duke University, gave a comprehensive overview of the path forward to an HIV vaccine. Whereas licensed vaccines allow infections to occur, and induce immune responses that are able to control and then clear infection, an HIV vaccine cannot act in this manner, due to the fact that once integrated, HIV cannot be cleared. Thus an HIV vaccine will likely have to completely prevent infection. To date the only mechanism by which this can be attained is through the induction of neutralizing antibody responses. However, these types of antibody responses only emerge in 15-20% of infected individuals and have yet to be elicited through an HIV vaccine. These types of antibodies likely only arise in a small fraction of infected individuals because these antibodies are highly mutated, potentially auto-reactive and eliminated by the immune system through tolerance mechanisms. However, 2 major events have re-invigorated the field. The first was the immune correlates analysis from the RV144 vaccine trial that showed a protective effect related to the induction of V1/V2-specific IgG antibodies in the absence of IgA responses against HIV that likely mediated protection through non-neutralizing or weakly-neutralizing mechanisms. The second signal has come from a flurry of studies that have recently identified a panel of new broadly neutralizing antibodies, that provide key clues regarding the viruses vulnerabilities. These neutralizing antibodies mark 4 regions of the viral envelope that represent the viruses “Achilles heel” that if targeted by a vaccine could provide protection from infection. To therefore design a vaccine that can elicit such antibodies, CHAVI-ID has now embarked on a “B cell lineage” targeted vaccine, that aims to define the mechanism(s) by which the 15% of HIV infected patients able to induce such protective antibodies attain this by mapping the evolution of B cell lineages over time to understand the path taken to mutate an antibody receptor to design novel vaccines that can induce this type of B cell immunity more rapidly. Coupled to mapping the evolution of the infecting virus, the 2 new CHAVI-IDs, in collaboration with many investigators world-wide, will develop novel vaccine approaches aimed at accelerating the speed of neutralizing antibody induction, that will hopefully provide sterilizing protection from HIV infection, providing an additional tool to promote many new AIDS free generations.

Track C report by Sinead Delany

This session offered the promise of future control of HIV transmission through vaccines or ART-based prevention, but reminded us that these advances will only be successful if the fundamental inequalities which drive HIV risk are also addressed.

Vaccines offer the potential as a powerful tool for the prevention of new infections and control of the epidemic. Dr Barton Haynes outlined how vaccine development has been invigorated by new findings on the immune correlates of protection generated by RV144 trial which has provided new hypotheses to test in future studies. New insights into broad neutralizing antibodies, their functions and the tolerance mechanisms that control their expression have led to the development of new strategies for vaccine design.

Dr Chewe Luo argued passionately that the goal of elimination of perinatal transmission of HIV will only be achieved if reductions in perinatal infections are combined with interventions to extend women's lives and reduce maternal mortality. Programmes that address the unmet need for family planning, that offer HIV prevention interventions to women, and that offer lifelong women to women infected with HIV are likely to have greater success. She highlighted the importance of expanding services to include the needs of couples, through couples counselling and testing.

Dr Rao Gupta contended that prevention of HIV infection in adolescents remains a key priority globally. The rapid succession of social and biological changes in adolescence put young girls at increased risk for HIV infection compared to boys. The reluctance of programmes to acknowledge girls as sexual beings has hampered access to commodities and services for those most at risk. Future programmes for youth will need target those most at risk, focus on educating girls, collect routine data that on adolescents in order to better monitor the epidemic in this largely hidden population, and engage adolescents as partners in the process. She and Louise Scruggs both highlighted the importance of addressing gender inequality if we are to turn to tide on transmission.

Track D report by Morten Skovdal

During this morning’s plenary session – on a day with a number of events and sessions addressing children and adolescents – Dr Chewe Luo (Senior Programme Adviser at UNICEF) delivered the presentation ‘Turning the tide on HIV in children and youth’. She addressed three key topic areas: elimination of MTCT, and keeping mothers alive; early diagnosis of infant diagnosis and the importance of treatment for HIV infected children; preventing HIV in adolescents, and providing treatment.

Since 1994 there has been evidence that providing ARV for pregnant women reduces HIV transmission to infants. The 2011 Global Plan for eliminating HIV in infants by 2015 has two overarching goals: 90% reduction in HIV infections in children; and a 50% reduction in HIV related mortality in women living with HIV during, or following pregnancy. There is much evidence supporting this global commitment, and studies confirming the preferred regimen for PMTCT, especially in the context of combining ARVs with breastfeeding.

Responses to this evidence have been “unprecedented”, resulting in a steady decline in the numbers of new infections in children globally. Between 2010-2011 for example, infections fell by an estimated10.8%. But, this falls short of the Global Plan’s May 2012 target of 25%. Future investment is required to ensure all targets are reached, which include: reducing HIV infection in women of childbearing age by 50%; reducing to zero unmet needs for family planning in women of childbearing age; and increase to 90% of ARV access for pregnant women living with HIV.

To ensure opportunities for prevention are not missed, Luo highlighted ways to improve the efficacy of PMTCT programmes. First, optimising the delivery of the most effective ARV regime; here, Malawi was pinpointed as the only country currently offering ‘Option B+’ (the provision of ARV regardless of the mother’s CD4), caused a ripple of audience applause. Second, introducing one treatment standard for HIV positive pregnant women to simplify delivery of optimal treatment. Third, integrating PMTCT and ARV services in Maternal Child Health and Community Services, by simplifying the regimen choice and approaches.

Luo also considered the issue of unmet family planning needs, which she suggests has “been stagnant” as an issue in the last decade, and highlighted the recent Gates Foundation, UNFPA, UK and US government commitments on family planning, which provide an opportunity to improve family planning access.

Turning the tide in children and youth also means scaling up care, treatment and support for infected children to reduce HIV related morbidity and mortality, and Luo reminded the audience that the Global Plan has as one target the provision of antiretroviral treatment (ART) to 100% of all children in need of treatment. She outlined a range of measures to achieve this: optimising the identification of infected children in early infancy; innovative technologies to simplify access to early infant diagnosis (EID) at the point of care, linking children into care and treatment; clinical studies to evaluate simplified dosing platforms to effect delivery of paediatric care and treatment in primary health care facilities.

Luo finished by considering adolescents. Understanding adolescent needs and vulnerabilities is critical to inform effective programming approaches for both HIV prevention and treatment. It is vital to decrease the vulnerability to HIV of adolescents – for example by enrolling and retaining girls in school; increasing the age of marriage; and ensuring social protection. Decreasing risk is also required, by measures such as: testing; offering treatment as required; harm reduction; and male circumcision.

Luo closed with a call to action. To ‘turn the tide’ on HIV in children and adolescents: treatment should be available for all HIV positive pregnant women using an optimal regime; innovative approaches to expand provider-initiated HIV testing to adolescents, pregnant women and their partners should be available; HIV testing and treatment early in infancy should be expanded; there must be collaboration with community groups; and adolescent programmes should focus on how to effectively deliver high impact interventions to have the best prevention and treatment benefit.

Track D report by Morten Skovdal

Dr Gita Rao Gupta (UNICEF), United States

This important presentation highlighted the imperative of addressing the multiple risks facing women and girls that increase their vulnerability to HIV. In particular, of the 4.8 million people aged 15-24 living with HIV, 3 million are female. Adolescence is a critical time of growth and maturation, and in regions where factors such as early marriage (younger than 18), early childbirth, and transactional sex (especially sub-Saharan Africa), adolescent girls face a range of challenges in negotiating successfully the transition into adulthood. Social, cultural and biological factors conspire to make adolescence “not a time of promise, but a time of peril.”

Gupta referred to the HIV Investment Framework as a useful tool for shaping policy and interventions to reduce the women and girls’ vulnerability, and proposed a number of specific recommendations for adolescent girls in particular: there should be a national plan in all countries to ensure girls are protected and empowered (and an acceptance that adolescents are likely to be sexually active); strategies must be in place to ensure girls are educated and remain in school; and adolescents must be visible in monitoring and routine data systems. It is also crucial to engage adolescents as partners in this process, for they “are experts in their own reality.”

Gupta closed with a quote from Anthony Lake, Executive Director of UNICEF: “We invest so much in keeping children alive in the first decade of life. We must not lose them in the second.”